Promoting inclusive recruiting and selection into military training schools: Admission waivers versus retesting.
There is high-level interest in diversifying workforces, which has led organizations-including the U.S. Armed Forces-to reevaluate recruiting and selection practices. The U.S. Coast Guard (USCG) has encountered particular difficulties in diversifying its workforce, and it relies mainly on the Armed Services Vocational Aptitude Battery (ASVAB) for assigning active-duty recruits to one of 19 specialized training schools. When recruits' scores fall below ASVAB entrance standards, the USCG sometimes offers admission waivers. Alternatively, recruits can retest until their ASVAB scores meet the entrance standard. Retesting has shown mixed results in the personnel selection literature, so our main interest is to determine whether retesting or waivers best support USCG recruits' training school outcomes, especially for recruits identifying as an underrepresented minority (URM). We use data from 16,624 USCG recruits entering between 2013 and 2021 and fit augmented inverse propensity weighted models to assess differences in training outcomes by pathway to admission while accounting for self-selection into pathways. Our analyses found (a) no difference in training outcomes between recruits who qualified from their initial scores and recruits who retested, (b) recruits who received waivers were less likely to complete training school on time and spent more time in remedial training when they failed training school compared to those who retested, and (c) improvement in training outcomes for retesting over waivers was larger for recruits identifying as an URM. Results suggest that retesting may be an effective strategy for workforce diversification and for improving outcomes among recruits identifying as an URM. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Isolation and identification of high-yielding alkaline phosphatase strain: a novel mutagenesis technique and optimization of fermentation conditions.
Isolating and screening enzyme-producing strains from microorganisms and the commercial production of ALPs from microorganisms are of increasing interest. In this work, isolation and identification of high-yielding alkaline phosphatase strain were carried out using atmospheric and room temperature plasma mutagenesis (ARTP) for optimization of fermentation conditions. A strain of alkaline phosphatase-producing bacteria was screened from soil and identified by 16S rRNA gene sequencing as Bacillus amyloliquefaciens and named S-1. This strain had an alkaline phosphatase activity of 2594.73 U/L. Later, mutagenesis breeding of the alkaline phosphatase-producing S-1 strain was conducted using (ARTP), from which a higher alkaline phosphatase-producing positive mutant strain S-52 was screened. A central combination of five factors, including corn starch, yeast extract, metal ions, fermentation temperature and inoculum ratio, was then used to influence the activity of alkaline phosphatase. Results from the response surface methodology showed that the maximum enzyme activity of alkaline phosphatase was 12,110.6 U/L at corn starch, yeast extract and magnesium ions concentrations of 17.48 g/L, 18.052 g/L and 0.744 g/L, respectively; fermentation temperature of 37.192 °C; and inoculation ratio of 5.59%. This study is important for further exploring ARTP mutagenesis in B. amyloliquefaciens and the commercialization of ALPs.


Effect of molecular configuration on binary diffusion coefficients of linear alkanes.
Mass diffusion coefficients are critically related to the predictive capability of computational combustion modeling. To date, the most common approach used to determine the molecular transport of gases is the Boltzmann transport equation of the gas kinetic theory. The Chapman-Enskog (CE) solution of this transport equation, combined with Lennard-Jones potential parameters, suggests a simple analytical expression for computing self and mutual diffusion coefficients. This approach has been applied over a wide range of flame modeling conditions due to its minimal computational requirement, despite the fact that the theory was developed only for molecules that have a spherical structure. In this study, we computed the binary diffusion coefficients of linear alkanes using all-atom molecular dynamics simulations over the temperature range 500-1000 K. The effect of molecular configurations on diffusion coefficients was determined relating the radii of gyration of the molecules to their corresponding collision diameters. The comparison between diffusion coefficients determined with molecular dynamics and the values obtained from the CE theory shows significant discrepancies, especially for nonspherical molecules. This study reveals the inability of CE theory with spherical potentials to account for the effect of molecular shapes on diffusion coefficients.


New Coumarinyl Ethers in Daphne oleoides Schreb. Collected from Sardinia Island.
The phytochemical analysis of the ethanolic extract obtained from D. oleoides collected from Sardinia Island allowed the isolation of several new constituents for the species (3, 8, and 9) together with two new coumarinyl ethers (1 and 2) besides the chemotaxonomic markers of the Daphne genus (4 - 7 and 10) which are also known to possess interesting biological activities. The structure of the new compounds were elucidated by extensive spectroscopic and spectrometric analyses. The identification of these compounds gives an experimental evidence of the variability in the secondary metabolites pattern owned by populations growing in restricted area in respect to populations not confined by geographical barrier.


Commercial cuts and chemical and sensory attributes of meat from crossbred Boer goats fed sunflower cake-based diets.
This study aimed to evaluate sunflower cake feed in commercial cut yields and chemical and sensory attributes of goat meat. Thirty-two castrated male goats were distributed in four levels (0, 8, 16 and 24%) of sunflower cake supplementation. The animals were slaughtered and the carcasses were placed in a cold chamber and sectioned into five anatomical regions corresponding to commercial cuts. Samples of the Longissimus lumborum muscle were analyzed for chemical composition and sensory quality. The chemical composition and pH were not affected by the treatments. The smell, taste and 'goatiness' of the aroma and flavor of the meat were also unaffected by the treatments. The appearance, tenderness and juiciness of the meat differed by treatment. The highest level (24%) of sunflower cake increased meat tenderness; however, according to the tasters there was reduced softness, although none of the samples were rejected by the tasters. Sunflower cake can be added to the diet at a level of up to 16% without altering the quantitative and qualitative attributes of the meat.


The "elfin face": craniofacial and dental aspects of the Williams-Beuren syndrome.
Williams Syndrome is a rare congenital disorder characterized by supravalvular aortic stenosis, peripheral pulmonary artery stenosis, mental retard and dysmorfic facial features. As regards the dental aspects of the syndrome, the deletion of the elastin gene induced clinicians to suspect periodontal alterations with a greater frequency of gingivo-periodontitis, but on the contrary no association between the syndrome and periodontal diseases have been found. Furthermore, patients show a higher frequency of teeth hypoplasia, an abnormal tooth morphology during primary dentition (12.5%) and during permanent dentition. We present a case report of a 12-year-old Caucasian boy affected by Williams-Beuren Syndrome who visited our hospital for a dental and orthodontic evaluation.


Accumulation of nonfunctional S-haplotypes results in the breakdown of gametophytic self-incompatibility in tetraploid Prunus.
The transition from self-incompatibility (SI) to self-compatibility (SC) is regarded as one of the most prevalent transitions in Angiosperm evolution, having profound impacts on the genetic structure of populations. Yet, the identity and function of mutations that result in the breakdown of SI in nature are not well understood. This work provides the first detailed genetic description of the breakdown of S-RNase-mediated gametophytic self-incompatibility (GSI) in a polyploid species that exhibits genotype-dependent loss of SI. Genetic analyses of six natural sour cherry (Rosaceae, Prunus cerasus) selections identified seven independent, nonfunctional S-haplotypes with disrupted pistil component (stylar-S) and/or pollen component (pollen-S) function. A genetic model demonstrating that the breakdown of SI in sour cherry is due to the accumulation of a minimum of two nonfunctional S-haplotypes within a single individual is developed and validated. Our finding that sour cherry is SI when only one nonfunctional S-haplotype is present has significant evolutionary implications since nonfunctional S-haplotypes would be maintained in the population without causing an abrupt shift to SC. Furthermore, we demonstrate that heteroallelic sour cherry pollen is self-incompatible, which is counter to the well-documented phenomenon in the Solanaceae where SC accompanying polyploidization is frequently due to the SC of heteroallelic pollen.


Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by down-regulation of SIRT1.
The effectiveness of Hsp90 inhibitors as anticancer agents was limited in multidrug-resistant (MDR) human cancer cells due to induction of heat shock proteins (Hsps) such as Hsp70/Hsp27 and P-glycoprotein (P-gp)-mediated efflux. In the present study, we showed that resistance to Hsp90 inhibitors of MDR human cancer cells could be overcome with SIRT1 inhibition. SIRT1 knock-down or SIRT1 inhibitors (amurensin G and EX527) effectively suppressed the resistance to Hsp90 inhibitors (17-AAG and AUY922) in several MDR variants of human lymphoblastic leukemia and human breast cancer cell lines. SIRT1 inhibition down-regulated the expression of heat shock factor 1 (HSF1) and subsequently Hsps and facilitated Hsp90 multichaperone complex disruption via hyperacetylation of Hsp90/Hsp70. These findings were followed by acceleration of ubiquitin ligase CHIP-mediated mutant p53 (mut p53) degradation and subsequent down-regulation of P-gp in 17-AAG-treated MDR cancer cells expressing P-gp and mut p53 after inhibition of SIRT1. Therefore, combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be a more effective therapeutic approach for Hsp90 inhibitor-resistant MDR cells via down-regulation of HSF1/Hsps, mut p53 and P-gp.


Perioperative Factors Aggravating Pharyngocutaneous Fistula After Total Laryngectomy: A Single-Center Retrospective Analysis Using the Clavien-Dindo Classification.
Pharyngocutaneous fistula formation represents a major postoperative complication following total laryngectomy. We aimed to investigate the risk factors for pharyngocutaneous fistula development after total laryngectomy and to identify factors that lead to severe cases of pharyngocutaneous fistula. Patients who underwent total laryngectomy between January 2013 and February 2021 were included in the study and were divided into 2 groups: Those with and without pharyngocutaneous fistula. The severity of pharyngocutaneous fistula was graded using the Clavien-Dindo classification. Patients with pharyngocutaneous fistula experienced longer operative time, greater intraoperative blood loss, greater decrease in perioperative hemoglobin level, and longer postoperative hospitalization. Unlike in lower-severity cases, patients with grade IIIb pharyngocutaneous fistula underwent preoperative radiotherapy or chemoradiotherapy; preoperative treatment was thus a risk factor for higher severity of pharyngocutaneous fistula (odds ratio, 35; P = 0.004). Salvage laryngectomy was found to be a predictor of severe pharyngocutaneous fistula development. Prolonged operative time, increased intraoperative blood loss, and decreased postoperative hemoglobin level were found to be predictors of postlaryngectomy pharyngocutaneous fistula formation.


Co-occurrence of autism, childhood psychosis, and intellectual disability associated with a de novo 3q29 microdeletion.
Some copy number variants (CNVs) are strongly implicated in both schizophrenia and autism spectrum disorders (ASDs). Childhood-onset schizophrenia (COS) occurs rarely with 0.1-1% of all schizophrenia diagnoses manifesting before age 10. 3q29 deletions are associated with both autism and schizophrenia, and are rare-the frequency of the deletion estimated to be 1 in 1,750 in developmental disorders. Only one patient with a 3q29 deletion was identified out of the first 1,174 families with ASDs included in the Simons Simplex Collection (SSC). We report on detailed clinical findings for this patient with a de novo 3q29 deletion who, as a young child, developed a very rare overlap of symptoms of both autism and early onset psychosis. His ASD was first diagnosed at the age of 4 years and his psychotic symptoms began at 5 years old. This is only the second case reported thus far of this rare event of co-occurring autism and very early onset psychosis in a child with a 3q29 deletion. It is also the earliest case of a child with autism developing comorbid psychosis-manifesting by the age of 5 years.


New laboratory tests in acute pancreatitis.
Acute pancreatitis (AP) is a common disease with wide variation of severity. The diagnosis of AP is usually based on high serum amylase or lipase values but the accuracy of these methods is considered unsatisfactory. One in five of the patients develops a severe disease and carries a considerable risk of development of organ failure and high mortality. Early detection of patients with severe AP and especially those with increased risk of organ failure is importance since such patients seem to benefit from treatment in an intensive care unit started as soon as possible after presentation. In addition to enzymological methods, increasing interest has been focused on laboratory markers reflecting the level of inflammatory response in AP. At present, in routine clinical work the most commonly used severity marker is serum C-reactive protein, the concentration of which rises too slowly to be used for early prediction of severity. New therapies aiming at modifying the course of systemic inflammation in AP are being developed and therefore monitoring the patient's immune inflammatory status is needed. In this review article we present the current knowledge of laboratory tests, which has been evaluated for diagnostic and prognostic purposes in AP.


Clearance of 3-methoxy-4-hydroxyphenylglycol from the cerebrospinal fluid.
The clearance of 3-methoxy-4-hydroxyphenylglycol (MHPG) from the cerebrospinal fluid of cats was studied. Both ventriculocisternal and cerebral subarachnoid perfusions demonstrated relatively high clearances that could not be blocked by probenecid. MHPG removal increased proportionally at all concentrations studied, suggesting diffusional clearance from cerebrospinal fluid. Bulk clearance accounted for only one-third of MHPG clearance from brain, and the likely mechanism of MHPG removal from the central nervous system is by diffusion to capillary blood. Differences between amine metabolites removed by mediated transport and diffusion are summarized, and it is suggested that a rapid unblockable diffusional clearance mechanism tends to make lumbar levels of MHPG a poor index of brain norepinephrine metabolism.


Study of the interaction of GB virus C/Hepatitis G virus fusion peptides belonging to the E2 protein with phospholipid Langmuir monolayers.
In order to determine the ability of 1,2-dipalmitoyl phosphatidylcholine (DPPC) and 1,2-dioleoyl phosphatidylglycerol (DOPG) to host peptide sequences belonging to the E2 protein of GBV virus C/Hepatitis G virus, the behaviour of Langmuir monolayers formed by these phospholipids and E2 (12-26), E2 (354-363) and E2 (chimeric) peptide sequences was analysed from data of surface pressure (π) versus area per molecule (A) isotherms, compression modulus (Cs-1), excess Gibbs energy of mixing (ΔGexc) and total Gibbs energy of mixing (ΔGmix). Three different behaviours were observed. Mixed films of E2 (12-26) with DPPC or DOPC showed negative values for the excess thermodynamic functions, and thus attractive interactions between mixed films components are greater than in ideal films. Mixtures of E2 (354-363) with DPPC or DOPG, exhibited positive values of excess functions, evidencing weaker interactions in the mixed films in relation to those of pure components. Finally, positive and negative excess functions were observed in E2 (chimeric)/DPPC or DOPG mixed films, depending on their composition. In short, the interaction between the phospholipids used in this work as models of cell membranes and E2 peptides varies with the type of phospholipid and the nature of the peptide (size, bulky, hydrophobicity and electric charge).


Root and Root Canal Anatomy of Primary Mandibular Central Incisor, Lateral Incisor, and Canine in Indian Children: A Cone Beam Computed Tomography Study.
A thorough knowledge of root and root canal morphology in primary dentition is essential for success of endodontic therapy. This information also finds importance in anthropological research in reconstructing human population history. Lack of studies of root and root canal morphology in mandibular anterior teeth prompted us to the present study. A total of 109 extracted primary mandibular incisors and canines were collected, out of which 90 teeth were selected for this study and divided into 3 groups: CI, mandibular central incisor; LI, mandibular lateral incisor; C, mandibular canine. All the sample teeth were scanned using cone beam computed tomography (CBCT). Number of roots, number of root canals, length of root, mesiodistal (MD), and buccolingual (BL) width of canal, shape of canal, and presence of accessory canals were assessed. Collected data were statistically compared using one-way ANOVA and chi-square tests. All teeth studied displayed single root with single root canal conforming to type I Vertucci's classification. Root length of CI was significantly shorter than both LI and C, with no significant difference between LI and C. Straight root canals were more common in CI and LI, whereas curved canals were more common in C. S-shaped canals were seen in a few CI and C. BL canal width was more than MD width in all teeth, C showing significantly larger dimensions than both CI and LI. This study presents root and root canal characteristics of primary mandibular central incisor, lateral incisor, and canine in children from Indian ethnicity.


Mosquito Innate Immunity.
Mosquitoes live under the endless threat of infections from different kinds of pathogens such as bacteria, parasites, and viruses. The mosquito defends itself by employing both physical and physiological barriers that resist the entry of the pathogen and the subsequent establishment of the pathogen within the mosquito. However, if the pathogen does gain entry into the insect, the insect mounts a vigorous innate cellular and humoral immune response against the pathogen, thereby limiting the pathogen's propagation to nonpathogenic levels. This happens through three major mechanisms: phagocytosis, melanization, and lysis. During these processes, various signaling pathways that engage intense mosquito⁻pathogen interactions are activated. A critical overview of the mosquito immune system and latest information about the interaction between mosquitoes and pathogens are provided in this review. The conserved, innate immune pathways and specific anti-pathogenic strategies in mosquito midgut, hemolymph, salivary gland, and neural tissues for the control of pathogen propagation are discussed in detail.


Neural dynamics in a model of the thalamocortical system. I. Layers, loops and the emergence of fast synchronous rhythms.
A large-scale computer model was constructed to gain insight into the structural basis for the generation of fast synchronous rhythms (20-60 Hz) in the thalamocortical system. The model consisted of 65,000 spiking neurons organized topographically to represent sectors of a primary and secondary area of mammalian visual cortex, and two associated regions of the dorsal thalamus and the thalamic reticular nucleus. Cortical neurons, both excitatory and inhibitory, were organized in supragranular layers, infraganular layers and layer IV. Reciprocal intra- and interlaminar, interareal, thalamocortical, corticothalamic and thalamoreticular connections were set up based on known anatomical constraints. Simulations of neuronal responses to visual input revealed sporadic epochs of synchronous oscillations involving all levels of the model, similar to the fast rhythms recorded in vivo. By systematically modifying physiological and structural parameters in the model, specific network properties were found to play a major role in the generation of this rhythmic activity. For example, fast synchronous rhythms could be sustained autonomously by lateral and interlaminar interactions within and among local cortical circuits. In addition, these oscillations were propagated to the thalamus and amplified by corticothalamocortical loops, including the thalamic reticular complex. Finally, synchronous oscillations were differentially affected by lesioning forward and backward interareal connections.


Metal ions control product specificity of isoprenyl diphosphate synthases in the insect terpenoid pathway.
Isoprenyl diphosphate synthases (IDSs) produce the ubiquitous branched-chain diphosphates of different lengths that are precursors of all major classes of terpenes. Typically, individual short-chain IDSs (scIDSs) make the C10, C15, and C20 isoprenyl diphosphates separately. Here, we report that the product length synthesized by a single scIDS shifts depending on the divalent metal cofactor present. This previously undescribed mechanism of carbon chain-length determination was discovered for a scIDS from juvenile horseradish leaf beetles, Phaedon cochleariae. The recombinant enzyme P. cochleariae isoprenyl diphosphate synthase 1 (PcIDS1) yields 96% C10-geranyl diphosphate (GDP) and only 4% C15-farnesyl diphosphate (FDP) in the presence of Co(2+) or Mn(2+) as a cofactor, whereas it yields only 18% C10 GDP but 82% C15 FDP in the presence of Mg(2+). In reaction with Co(2+), PcIDS1 has a Km of 11.6 μM for dimethylallyl diphosphate as a cosubstrate and 24.3 μM for GDP. However, with Mg(2+), PcIDS1 has a Km of 1.18 μM for GDP, suggesting that this substrate is favored by the enzyme under such conditions. RNAi targeting PcIDS1 revealed the participation of this enzyme in the de novo synthesis of defensive monoterpenoids in the beetle larvae. As an FDP synthase, PcIDS1 could be associated with the formation of sesquiterpenes, such as juvenile hormones. Detection of Co(2+), Mn(2+), or Mg(2+) in the beetle larvae suggests flux control into C10 vs. C15 isoprenoids could be accomplished by these ions in vivo. The dependence of product chain length of scIDSs on metal cofactor identity introduces an additional regulation for these branch point enzymes of terpene metabolism.


Characterization of food binding of vitamin B-6 in orange juice.
There is substantial evidence that natural vitamin B-6 exists largely in a bound form. It has been shown that the principal modes of binding represents an interaction of pyridoxal and/or pyridoxal phosphate with protein moieties. The nature and extent of binding of different forms of the vitamin in orange juice was investigated. Studies employing ultracentrifugation, ultrafiltration and, membrane dialysis of this food product suggested binding to a molecule of less than 3,500 daltons molecular weight. Binding was resistant to protease treatment although susceptible to heat-acid hydrolysis. Separation of pyridoxal, pyridoxine, and pyridoxamine species of the vitamin by ion exchange chromatography was followed by fluorometric analysis with and without preparative hydrolysis. Extensive and equal binding of both pyridoxal and pyridoxine was observed by this method. Thus, the binder(s) of vitamin B-6 in orange juice is a small dialyzable molecule which is heat stable, binds both pyridoxal and pyridoxine and is non-protein in nature.


The Minimum Data Set bedfast quality indicator: differences among nursing homes.
Excessive time in bed has negative effects on both physical conditioning and functioning. There are no data or practice guidelines relevant to how nurses should manage the in-bed times of nursing home residents, although all nursing homes receive a bedfast prevalence quality indicator report generated from the Minimum Data Set. To compare nursing homes that score in the upper and lower quartiles on the Minimum Data Set bedfast prevalence quality indicator for proportion of bedfast residents, activity and mobility nursing care, and amount of time all residents spend in bed, and to evaluate whether residents who spend more time in bed are different from those who spend less time in bed according to functional measures. A cohort design used medical records, resident interviews, and direct observation data to compare 15 nursing homes (n = 451 residents) on the proportion of bedfast residents, the amount of time residents spent in bed, the frequency of activity, and the scores on six activity and mobility care process indicators. Significant differences were found between upper (i.e., higher prevalence of bedfast residents) and lower quartile nursing homes in the proportion of time residents were observed in bed (43% vs. 34%, respectively; p =.007), and in the proportion of residents who spent more than 22 hours in bed per day (18% vs. 8%, respectively; p =.002). All nursing homes underestimated the number of bedfast residents. The residents of upper quartile homes showed more activity episodes and reported receiving more walking assistance than the residents of lower quartile homes. Minimum Data Set bedfast quality indicator identified nursing homes in which residents spent more time in bed, but did not reflect differences in activity and mobility care. In fact, upper quartile homes provided more activity and mobility care than lower quartile homes. Across all the nursing homes, most of the residents spent at least 17 hours a day in bed. Further study of activity and mobility care and bedfast outcomes in nursing homes is needed, and nurses need to note the amount of time nursing home residents spend in bed.


Lung cancer risk among Czech tin and uranium miners--comparison of lifetime detriment.
First epidemiological evidence of lung cancer risk from exposure to radon was based on studies of uranium miners. The risk in other mines was reported later. The cohort study among 2466 Czech tin miners was conducted in order to estimate the size of the risk and to compare it to that in uranium mines. Based on 205 lung cancers, the estimate of excess relative risk per unit exposure in the simple linear model 0.011 is compatible with findings from two cohort studies of Czech uranium miners. This similarity holds in more complex models that include modifying effects of age and time since exposure. In addition, an alternative description of the risk in terms of lifetime risk was used. This approach provides summarized characteristics, in which modifying effects of time and age are incorporated. The attributive risk derived from the lifetime relative risk is proportional to cumulated exposure observed in both tin and uranium miners. On the other hand, the expected life shortening of 19 years among radiation induced deaths is similar in these studies.


Initiation of spontaneous epileptiform events in the rat neocortex in vivo.
We used voltage-sensitive dye imaging to visualize the distribution of initiation sites of the spontaneous interictal-like spikes (sISs) in rat neocortex, in vivo, induced by bicuculline or picrotoxin over the exposed cortex. The initiation site was small (approximately 200 microm diam). On average each initiation site initiated 2.0 +/- 0.8 sISs (9 animals, 499 sISs, 251 sites). This is significantly different from that in neocortical slices, where each initiation site initiated 30-100 sISs. The initiation sites were not randomly distributed. The distance between two consecutive sites tended to be either <800 or >1200 microm, suggesting a temporal "suppression annulus" surrounding each initiation site. Within the annulus, the likelihood for initiating the next sIS was reduced. Suppression annulus did not have a noticeable change in the presence of GABA(b) antagonist, suggesting it did not depend on the GABA(b) inhibition. We also applied bicuculline locally to a spot of 800 x 800 microm(2) for approximately 45 min. During this period approximately 1000 sISs occurred within the spot. Bicuculline or picrotoxin was then applied to the entire craniotomy window. The pretreatment created an obvious cluster of initiation sites. Around this cluster, the suppression annulus became obvious in individual animals. Our results suggest that, in disinhibited cortex, epileptiform events were initiated from small sites. The initiation sites may cluster in an area with increased local activity. Surrounding each initiation site there may be a temporal suppression annulus.


Juvenile waiting stage crown-of-thorns sea stars are resilient in heatwave conditions that bleach and kill corals.
The juveniles of predatory sea stars can remain in their recruitment-nursery habitat for some time before their ontogenetic shift to the adult habitat and diet. These small juveniles are vulnerable to a range of factors with their sensitivity amplified by climate change-driven ocean warming. We investigate the thermal tolerance of the waiting stage herbivorous juveniles of the keystone coral predator, the crown-of-thorns sea star (COTS, Acanthaster sp.), in context with the degree heating weeks (DHW) model that predicts coral bleaching and mass mortality. In temperature treatments ranging from +1 to 3°C in prolonged heatwave acclimation conditions, the juveniles exhibited ~100% survival in DHW scenarios that trigger coral bleaching (4 DHW), resulting in mass mortality of corals (8 DHW) and extreme conditions well beyond those that kill corals (12 DHW). This indicates that herbivorous juvenile COTS are far more resistant to heatwave conditions than the coral prey of the adults. The juveniles exhibited higher activity (righting) and metabolic rate after weeks in increased temperature. In separate acute temperature experiments, the upper thermal limit of the juveniles was 34-36°C. In a warming world, juvenile COTS residing in their coral rubble nursery habitat will benefit from an increase in the extent of this habitat due to coral mortality. The juveniles have potential for long-term persistence as herbivores as they wait for live coral to recover before becoming coral predators, thereby serving as a proximate source of COTS outbreaks on reefs already in a tenuous state due to climate change.


Approaches to advancing quantitative human health risk assessment of environmental chemicals in the post-genomic era.
The contribution of genomics and associated technologies to human health risk assessment for environmental chemicals has focused largely on elucidating mechanisms of toxicity, as discussed in other articles in this issue. However, there is interest in moving beyond hazard characterization to making more direct impacts on quantitative risk assessment (QRA)--i.e., the determination of toxicity values for setting exposure standards and cleanup values. We propose that the evolution of QRA of environmental chemicals in the post-genomic era will involve three, somewhat overlapping phases in which different types of approaches begin to mature. The initial focus (in Phase I) has been and continues to be on "augmentation" of weight of evidence--using genomic and related technologies qualitatively to increase the confidence in and scientific basis of the results of QRA. Efforts aimed towards "integration" of these data with traditional animal-based approaches, in particular quantitative predictors, or surrogates, for the in vivo toxicity data to which they have been anchored are just beginning to be explored now (in Phase II). In parallel, there is a recognized need for "expansion" of the use of established biomarkers of susceptibility or risk of human diseases and disorders for QRA, particularly for addressing the issues of cumulative assessment and population risk. Ultimately (in Phase III), substantial further advances could be realized by the development of novel molecular and pathway-based biomarkers and statistical and in silico models that build on anticipated progress in understanding the pathways of human diseases and disorders. Such efforts would facilitate a gradual "reorientation" of QRA towards approaches that more directly link environmental exposures to human outcomes.


[Methodologic aspects of modern, computerized ergospirometry (CPX): ramp program, constant workload test and CO2 rebreathing method].
The cardiopulmonary exercise testing (CPX) is a non-invasive method for the evaluation of the cardiopulmonary exercise capacity. Based upon the recent technical progress in gas analysers and personal computers today it is possible to perform CPX with acceptable time consumption, high practicability and high reproducibility of the results in many clinical areas. CPX is realized on a bike or on a treadmill. In bicycle CPX a ramp program (increase of x watts per minute) or a constant workload test (p.e. with 75% of the watts at anaerobic threshold) are performed. Furthermore, an estimation of the cardiac output using CO2-rebreathing method can be realized during a ramp program or a constant workload test. In this paper, also the CPX parameters of the ramp program, the constant workload test and the CO2-rebreathing method are defined and explained. The normal values of CPX are dependent of age, sex, body weight and exercise program. This should be kept in mind in interpreting the measured CPX data. Additionally, the performance of a routine CPX will be reported. Furthermore, the accuracy of the CPX parameters and the potential influences on the data will be discussed. Finally, problems during measurements and their analysis will be clarified.


Methylation quantitative trait loci within the TOMM20 gene are associated with metabolic syndrome-related lipid alterations in severely obese subjects.
The TOMM20 gene was previously identified as differentially expressed and methylated between severely obese subjects with and without metabolic syndrome (MS). Since metabolic complications do not affect all obese patients to the same extent, the aim of this study was to identify methylation quantitative trait loci (meQTL) potentially associated with MS-related complications within the TOMM20 locus. Methylation profiling, SNP genotyping and meQTL association tests (general linear models) were performed in a population of 48 severely obese subjects. Genotyping was extended to a larger population of 1720 severely obese subjects with or without MS, where genotype- and diplotype-based association tests were assessed by logistic regression. In silico analyses were performed using TRAP. Four SNPs were identified as significant meQTLs for the differentially methylated site cg16490124. Individuals carrying rare alleles of rs4567344 (A > G) (P = 4.9 × 10(-2)) and rs11301 (T > C) (P = 5.9 × 10(-3)) showed decreased methylation levels at this site, whereas those carrying rare alleles of rs4551650 (T > C) (P = 3.5 × 10(-15)) and rs17523127 (C > G) (P = 3.5 × 10(-15)) exhibited a significant increase in methylation. rs4567344 and rs11301 were associated with increased susceptibility to exhibit high plasma triglycerides (TG ≥ 1.69 mmol/L), while rare alleles of rs4551650 and rs17523127 were significantly more represented in the low plasma total-C group (total-C ≤ 6.2 mmol/L). Haplotype reconstruction with the four meQTLs (rs4567344, rs11301, rs4551650, rs17523127) led to the identification of ten different diplotypes, with H1/H2 (GCGG/ACGG) exhibiting a nearly absence of methylation at cg16490124, and showing the highest risk of elevated plasma TG levels [OR = 2.03 (1.59-3.59)], a novel association with elevated LDL-cholesterol [OR = 1.86 (1.06-3.27)] and the complete inversion of the protective effect on total-C levels [OR = 2.03 (1.59-3.59)], especially in men. In silico analyses revealed that rs17523127 overlapped the CpG site cg16490124 and encompassed the core binding sites of the transcription factors Egr 1, 2 and 3, located within the TOMM20 promoter region. This study demonstrates that TOMM20 SNPs associated with MS-related lipid alterations are meQTLs potentially exerting their action through a CpG methylation-dependent effect. The strength of the diplotype-based associations may denote a novel meQTL additive action and point to this locus as particularly relevant in the inter-individual variability observed in the metabolic profiles of obese subjects.


Recurrent allopolyploidizations diversify ecophysiological traits in marsh orchids (Dactylorhiza majalis s.l.).
Whole-genome duplication has shaped the evolution of angiosperms and other organisms, and is important for many crops. Structural reorganization of chromosomes and repatterning of gene expression are frequently observed in allopolyploids, with physiological and ecological consequences. Recurrent origins from different parental populations are widespread among polyploids, resulting in an array of lineages that provide excellent models to uncover mechanisms of adaptation to divergent environments in early phases of polyploid evolution. We integrate here transcriptomic and ecophysiological comparative studies to show that sibling allopolyploid marsh orchid species (Dactylorhiza, Orchidaceae) occur in different habitats (low nutrient fens vs. meadows with mesic soils) and are characterized by a complex suite of intertwined, pronounced ecophysiological differences between them. We uncover distinct features in leaf elemental chemistry, light-harvesting, photoprotection, nutrient transport and stomata activity of the two sibling allopolyploids, which appear to match their specific ecologies, in particular soil chemistry differences at their native sites. We argue that the phenotypic divergence between the sibling allopolyploids has a clear genetic basis, generating ecological barriers that maintain distinct, independent lineages, despite pervasive interspecific gene flow. This suggests that recurrent origins of polyploids bring about a long-term potential to trigger and maintain functional and ecological diversity in marsh orchids and other groups.


Modification of cadaverine content by NO in salt-stressed maize.
NO has an important role in the control of plant development, growth, and the response to abiotic stress. In our recent paper it was demonstrated that NO affected the salt-induced changes in free amino acid levels in maize. (1) Since polyamines are synthesized from lysine and arginine, it was supposed that their concentrations are also influenced by NO. Cadaverine levels were increased by a NO donor and decreased by an inhibitor of NO synthesis in salt-stressed maize. These findings indicate that NO participates in the mediation of the effect of salt on cadaverine content. The coordinated changes in the NO and cadaverine levels may be involved in regulating of the response to salt stress in maize.


Induced apoptosis of TH2 lymphocytes in asthmatic children treated with Dermatophagoides pteronyssinus immunotherapy.
Allergen-specific immunotherapy (IT) has been effectively used for the treatment of asthma. Allergen specific IT induced immune tolerance with induction of TH2 cells anergy remain to be clarified. The aim of this study was to evaluate whether the mite allergen Dermatophagoides pteronyssinus (Dpt) specific IT serially decreased IL-4+/CD4+ (TH2) lymphocytes and induced apoptosis of TH2 lymphocytes in asthmatic children. Sixty Dpt-sensitive asthmatic children were randomly assigned to a received IT and an untreated group. Dermatophagoides pteronyssinus specific IT treated patients were examined at three time points: before IT, after 6 months of an increased dose phase and with maximum tolerated doses after 1 yr. Peripheral blood mononuclear cells (PBMC) were isolated and cultured for 48 h for cellular staining with CD4+, CD45RO cell phenotypes and interleukin (IL)-4 and interferon-gamma expression by fluorescence monoclonal antibodies. Apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. A simultaneous flow cytometric study using the same permeabilized cell was examined to determine whether apoptosis occurred preferentially in TH2 lymphocytes. The data demonstrated that Dpt specific IT decreased Dpt-specific IgE levels (p < 0.01) after 1 yr of treatment. In addition, decreased CD4+IL-4+ TH2 cells with increased CD4+IFN-gamma+ TH(1) cells were observed at 6 months and 1 yr after IT treatment (p < 0.05). At the same time, apoptosis of CD4+IL-4+ TH2 lymphocytes in the IT group had increased after 1 yr of treatment when compared with the results before treatment (p < 0.001) and after 6 months of treatment (p = 0.046). In addition, CD45RO cells apoptosis mainly occurred after 6 months of IT treatment and after 1-year period of IT treatment (p < 0.05). All of the data suggested that Dpt specific IT decreased Dpt specific IgE and CD4+IL-4+ TH2 lymphocytes with induction apoptosis of CD4+IL-4+ TH2 lymphocytes subsets serially.


The Concussion Toolbox: The Role of Vision in the Assessment of Concussion.
Concussion may lead to subtle changes in brain function, and tests involving the visual system probe higher cortical functioning and increase our sensitivity in detecting these changes. Concussions are acutely and sometimes more persistently associated with abnormalities in balance, cognition, and vision. The visual system involves roughly half of the brain's circuits, including many regions susceptible to head impacts. After a concussion, the neuro-ophthalmologic exam commonly detects abnormalities in convergence, accommodation, the vestibulo-ocular reflex, ocular muscle balance, saccades, and pursuit. The King-Devick (K-D) test is a visual performance measure that may increase the sensitivity of detecting concussions on the sideline when used in combination with tests of cognition and balance that are part of the Sports Concussion Assessment Tool (3rd ed.; SCAT3). Portable eye movement trackers and pupillometry may in the future improve our neuro-ophthalmic assessment after concussions. Combining visual tasks with neuroimaging and neurophysiology has allowed subtle changes to be detected, may refine our ability to make appropriate return-to-play decisions, and could potentially determine susceptibility to long-term sequelae of concussion.


Benefit of simultaneous recording of EEG and MEG in dipole localization.
In this study, we tried to show that EEG and magnetoencephalography (MEG) are clinically complementary to each other and that a combination of both technologies is useful for the precise diagnosis of epileptic focus. We recorded EEGs and MEGs simultaneously and analyzed dipoles in seven patients with intractable localization-related epilepsy. MEG dipoles were analyzed by using a BTI Magnes 148-channel magnetometer. EEG dipoles were analyzed by using a realistically shaped four-layered head model (scalp-skull-fluid-brain) built from 2.0-mm slice magnetic resonance imaging (MRI) images. (a) In two of seven patients, MEG could not detect any epileptiform discharges, whereas EEG showed clear spikes. However, dipoles estimated from the MEG data corresponding to the early phase of EEG spikes clustered at a location close to that of the EEG-detected dipole. (b) In two of seven patients, EEG showed only intermittent high-voltage slow waves (HVSs) without definite spikes. However, MEG showed clear epileptiform discharges preceding these EEG-detected HVSs. Dipoles estimated for these EEG-detected HVSs were located at a location close to that of the MEG-detected dipoles. (c) Based on the agreement of the results of these two techniques, surgical resection was performed in one patient with good results. Dipole modeling of epileptiform activity by MEG and EEG sometimes provides information not obtainable with either modality used alone.


Sonographic detection of prenatal liver mass.
Ultrasound examination is now performed on about 30% of all pregnancies. Although it is used primarily to estimate gestational age, viability, presentation, and placental site, detailed fetal anatomy is also disclosed. Many abnormalities are now detected prenatally which may not be clinically apparent at birth, and raise new dilemmas of patient management. We describe a large mass documented by ultrasound in the right lobe of liver in a 29-week-old fetus. Subsequent postnatal investigation confirmed the initial ultrasound findings and documented spontaneous regression.


Use of a computer-based simulated consultation tool to assess whether doctors explore sociocultural factors during patient evaluation.
The delivery of patient-centred care to diverse populations requires that doctors identify sociocultural factors that may affect care. We adapted a computer-based simulated consultation tool and tested its utility for assessing whether doctors explore sociocultural factors during a patient evaluation, and whether they include such information in their case conclusions and follow-up recommendations. We developed two detailed patient 'stories' that involved sociocultural issues that doctors needed to identify and consider for adequate clinical management. They were incorporated into an existing 'Virtual Internet Patient Simulation' (VIPS) program designed to test clinical reasoning skills. Doctors and medical students (n = 618) were invited to access the program via Internet. For each consultation, participants were assigned a sociocultural score, corresponding to the number of sociocultural domains explored. Scores were then compared with subjective ratings of participants' performance by expert doctors. 118 respondents completed at least one virtual consultation (19%), 92 conducted both. The mean number of sociocultural dimensions explored by doctors (i.e. sociocultural score) was 3.9 (standard deviation 2.6) for case 1, and 5.2 (standard deviation 2.3) for case 2. The two sociocultural scores were moderately correlated (Spearman r = 0.65, P < 0.001). Sociocultural scores correlated positively with experts' subjective ratings of participants' performance (Spearman r = 0.84 for case 1 and 0.78 for case 2, both P < 0.001). The adapted computer-based simulated consultation tool provided a feasible means to assess doctors' exploration of sociocultural issues during a clinical evaluation. Further validation of this method should be conducted by comparing VIPS results with other skills assessment methods such as objective structured clinical examination or direct observation of clinical performance.


Familial occurrence of abdominal aortic aneurysms.
The occurrence of clinically diagnosed and ruptured abdominal aortic aneurysms (AAAs) in the family was studied retrospectively among 200 consecutive patients with AAAs treated at the Surgical Clinic, University Hospital of Umeå, in the north of Sweden, during the period 1965 to 1981. A standardized questionnaire was sent to the 89 patients who were still alive when the study was performed, and 87 patients answered it. In 14 of these families there was one blood relative with AAA, and in two families there were two blood relatives with AAAs, apart from the proband. In nine cases AAAs occurred among the 468 brothers and sisters of the probands (1.9%), and in five cases among cousins. Seven of the 204 deceased brothers and sisters (3.4%) had died of ruptured AAAs. No questionnaires were sent to the families of the 111 deceased patients, but at least 11 of these patients had AAAs in the family. Pedigrees of the families with aggregation of aneurysms are presented, and fortuitous familial aggregation or predisposition to the development of AAAs is discussed.


Distinctive antioxidant and antiinflammatory effects of flavonols.
The antioxidant and antiinflammatory effects of flavonols have been suggested to be structure-related. Results revealed that selected flavonols, including fisetin (F), kaempferol (K), morin (MO), myricetin (MY), and quercetin (Q), exhibited distinctive free radical scavenging properties against different kinds of free radicals. The H donation (DPPH bleaching) potential was Q > F approximately equals MY > MO > K, indicating that the presence of a 3',4'-catechol moiety in the B ring correlated with high activity. The 4'-OH in the B ring was suggested to be important for reducing xanthing/xanthine oxidase-generated superoxide; while an additional OH moiety on the ortho sites (3' or 5') attenuated the effect as the observed inhibitory potency was K approximately equals MO > Q > F > MY. The relative inhibitory effect for Fenton-mediated hydroxyl radical was K approximately equals MO approximately equals Q > F > MY. This result implies the involvement of 4-keto, 5-OH region in Fe++ chelating and the negative effect of pyrogallol moiety in the B ring. Similar to the inhibitory activity against a N-formyl-methionyl-leucyl-phenylalanine (f-MLP)-stimulated oxidative burst in human polymorphonuclear neutrophils (PMN), our result showed that the structural peculiarity of the di-OH in the B ring obviously rendered F, Q, and MO more potent as ROS inhibitors than MY and K, which have tri- and mono-OH in the B ring, respectively. All of the previous data indicated that the structure prerequisite to reinforce the free radical scavenging activity varies with the type of free radical. We further analyzed the effects of flavonols on nitric oxide (NO) production in endotoxin-stimulated murine macrophages, RAW264.7 cells. Results showed that all flavonols (up to 10 microM) inhibited NO production without exerting detectable cytotoxicity. F, K, and Q dose-dependently repressed iNOS mRNA expression and prostaglandin E2 (PGE2) production, in part through an attenuating NF-kappaB signaling pathway. This result indicates that flavonols, despite structural similarity, have different antioxidant and antiinflammatory effects.


The relationship between scholastic progress and nutritional status. Part I. A study of 488 school beginners.
The reading progress of 488 Chatsworth Indian school beginners, in relation to their nutritional status, was assessed. It was found that the majority of the children were grossly growth-retarded and some 90% of them could be classified as slow learners. The significance of these findings is discussed. It is recommended that dietary supplementation be introduced for preschool as well as for school-going children in communities where growth retardation is prevalent.


[Anticoagulation and chronic hemodialysis].
The application of effective hemodialysis in humans was delayed until the development of cellulose-based membranes in 1940s, and the advent of heparin as the primary means of anticoagulation. Unfractionated heparin is still the most commonly used agent for anticoagulation, but its potentially serious complications, such as hemorrhage and heparin-induced thrombocytopenia type II, led the scientific community to consider other options to counteract coagulation. ''Low heparin dialysis'', ''heparin-free dialysis'', regional heparinization, low molecular weight heparins, citrate, prostacyclin, nafamostat, low molecular weight heparanoid and direct thrombin inhibitors are among these methods and have different safety, efficacy and cost. In general, hemodialysis patients with active hemorrhage or at high risk for bleeding complications are best treated with heparin-free hemodialysis. Low molecular weight heparanoid and direct thrombin inhibitors (recombinant hirudin or argatroban) may be useful for anticoagulation of the extracorporeal circuit in the rare patients with confirmed heparin-induced thrombocytopenia type II, who cannot be dialyzed with heparin.


[Expression of melanoma-associated antigen-C2 in breast cancers and mechanism].
Objective: To analyze the expression pattern, mechanism and clinical significance of melanoma-associated antigen-C2 (MAGE-C2) in tumor-free breast specimens, breast benign disease specimens and breast cancer specimens. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expressions of MAGE-C2 in 60 tumor-free breast specimens, 60 breast benign disease specimens and 60 breast cancer specimens. The correlation of MAGE-C2 expression with clinicopathological parameters and prognosis of breast cancer patients were analyzed. The expression of MAGE-C2 was also detected by RT-PCR in breast cancer cell MCF-7 and MDA-MB-231 treated with DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA). Results: The positive expression rates of MAGE-C2 mRNA and protein were 61.7% (37/60) and 58.3% (35/60) in breast cancer specimens, respectively, while negative expressed in breast and begin disease specimens. MAGE-C2 protein expression was associated with tumor grade, histological type and blood vessel invasion of breast cancer patients (P<0.05). The incidence of recurrence-free survival of patients with positive MAGE-C2 expression were lower than that of patients with negative MAGE-C2 expression (P<0.05). Multivariate Cox regression analysis showed that the clinical stage (P<0.01), lymph node metastasis (P<0.05) and MAGE-C2 expression (P<0.05) were the independent prognostic factors of breast cancer patients. The MAGE-C2 mRNA was not observed in the control and TSA treated breast cancer cells while upregulated in the 5-aza-CdR treated cells. Besides, 5-aza-CdR combined with TSA further enhanced MAGE-C2 mRNA level in breast cancer cells (P<0.05). Conclusions: MAGE-C2 is one of the tumor-specific antigen and its expression is related with the poor prognosis of breast cancer patients. DNA methylation and histone acetylation may be an important regulation mechanism of MAGE-C2 gene expression.


Analysis of Clinical-Pathological Data with Impact on Overall Survival in Male Breast Carcinoma: An International Multi-Institutional Study of 217 Cases.
Background: The aim of this study was to evaluate clinical-pathological parameters with impact on overall survival (OS) in male breast carcinoma (MBC). Methodology: We assessed OS at 5 years and at 10 years respectively, as well as OS according to age, tumor size, microscopic type, histological grade, axillary lymph node status, and molecular profile. Results:Two hundred seventeen cases, with a mean age of 62 (range: 18- 85), right breast involvement (52.53%), invasive carcinoma of no special type (86.63%), G2 histological grade (55.4%), T2 (54.41%), N+ (65.89%) and Luminal A molecular subtype (85.29%) were identified. ER, PR and AR were positive in 89.71%, 83.82% and 93.29% of cases, respectively. HER2 was overexpressed in 8.33% of cases and a high Ki67 proliferation index was present in 75% of cases. The 5-year OS was 67.2%, whereas 10-year OS was 48.5%; OS was 92.7% at 5 years and 73.8% at 10 years in axillary lymph node (LN) negative cases, while OS was 59.7% at 5 years and 41.3% at 10 years in axillary LN positive cases (p=0.003). Conclusions: Age at diagnosis ( 60 years), larger tumor size, presence of LN metastases and absence of oncological treatment are negative factors influencing prognosis, with only axillary LN status (p=0.005) and triple negative molecular profile (p=0.05) being statistically significant unfavorable independent prognostic parameters in a multivariate analysis.


Cyclometallated platinum(II) complexes of benzylidene-2,6-di-isopropylphenylamine containing bidentate phosphines: synthesis, structural properties and reactivity studies.
The reaction of the cyclometallated complex [PtCl(N^C)(dmso)], 1 (N^C represents the cyclometallated Schiff base, benzylidene-2,6-diisopropylphenylamine), with 1,1'-bis(diphenylphosphino)ferrocene, dppf, bis(diphenylphosphino)methane, dppm, or 1,2-bis(diphenylphosphino)ethane, dppe, in a 2 : 1 ratio or an equimolar ratio using acetone as the solvent produced the corresponding binuclear or mononuclear diphosphine platinum complexes. In the case of the mononuclear complexes, the diphosphines act as either a bidentate ligand or a monodentate ligand depending on the size of the bite angle of the diphosphines, while in the case of the binuclear complexes, the diphosphines act as a bridging ligand between the two metal centres. The solid state structures of some of the binuclear as well as mononuclear species are reported. The mononuclear derivatives were found to show different behaviour in solution and in the solid state when compared to the binuclear analogues. This behaviour is also influenced by the nature of the diphosphine ligands employed.


The cage design affects intermale aggression in small groups of male laboratory mice: strain specific consequences on social organization, and endocrine activations in two inbred strains (DBA/2J and CBA/J).
Effects of the enrichment of conventional laboratory housing cages with an additional labyrinth on intermale aggression, social organization, and activations of the pituitary-adrenocortical and sympathetic-adrenomedullary neuroendocrine subsystems are compared between adult male DBA/2J and CBA/J mice, differing genetically in their intermale aggression. Mice of both strains were kept three per cage for six weeks either in standard laboratory cages (SC) or in enriched cages (EC). Intermale aggression against a strange intruder and between cagemates was monitored once a week within each group. Dominance relations were derived from the distribution of attacks within a group. Plasma corticosterone titers (PCT) and activities of the tyrosinehydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were determined for each mouse at the end of the study. The main findings were: 1. Intermale aggression increased in both strains in groups kept in EC. 2. In the more aggressive DBA/2J the pattern of social organization shifted from groups with a single permanent dominant mouse in SC to groups with a frequently changing dominant mouse in EC. 3. In CBA interchanges of the dominant mouse was prevailing and did not differ between the two housing conditions. 4. In DBA/2J mice PCT were significantly elevated in EC. 5. In CBA/J mice activities of TH and PNMT were significantly elevated in EC. 6. Body weight gain was significantly delayed in mice kept in EC in both strains. Findings revealed strainspecific environmental effects on both social organization and endocrine states. The PCT increase obtained only in DBA/2J indicate that alterations of the social relations between cagemates are more likely to induce states of stress than an increase in intermale aggression alone.


Rapid prediction of need for hospitalization in acute asthma.
Sixty-seven episodes of acute asthma were treated in an emergency room. The characteristics of the attacks and subsequent course were then analyzed to determine criteria that could be used for an early decision in regard to the need for hospitalization. Attacks that were not successfully treated in the emergency room were most often characterized by very severe obstruction and a poor response to an initial injection of epinphrine. It is suggested that severely obstructed patients (peak flow less than 16% of predicted) whose peak flow remains less than 60 liters/min, or who exhibit a less than 16% improvement following 0.3 ml epinephrine, be promptly admitted.


External validation of the GRACE risk score and the risk-treatment paradox in patients with acute coronary syndrome.
To validate the Global Registry of Acute Coronary Events (GRACE) risk score and examine the extent and impact of the risk-treatment paradox in contemporary patients with acute coronary syndrome (ACS). Data from 5015 patients with ACS enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for model validation. The performance of the GRACE risk score for predicting in-hospital and 1-year mortality was evaluated based on indices of model discrimination and calibration. Differences in the delivery of guideline-recommended care among patients who survived hospitalisation (n=4911) per GRACE risk stratum were assessed and the association with postdischarge mortality was examined. Discriminative power of the GRACE risk score was good for predicting in-hospital (c-statistic: 0.86; 95% CI: 0.83 to 0.90) and 1-year mortality (c-statistic: 0.82; 95% CI: 0.79 to 0.84). However, the GRACE risk score overestimated the absolute in-hospital and 1-year mortality risk (Hosmer-Lemeshow goodness-of-fit test p<0.01). Intermediate-risk and high-risk patients were 12% and 29% less likely to receive optimal guideline-recommended care compared with low-risk patients, respectively. Optimal guideline-recommended care was associated with lower mortality in intermediate- and high-risk patients. The GRACE risk score identified patients at higher risk for in-hospital and 1-year mortality, but overestimated absolute risk levels in contemporary patients. Optimal guideline-recommended care was associated with lower mortality in intermediate-risk and high-risk patients, but was less likely to be delivered with increasing mortality risk.


Exploring the strategies that midwives in British Columbia use to promote normal birth.
Rates of normal birth have been declining steadily over the past 20 years, despite the evidence of the benefits to mother and baby. This is most obvious in steadily increasing caesarean section rates across countries and studies of the factors involved suggest it may be more to do with the organization of maternity care and the preferences of healthcare providers than changes in maternal or demographic conditions. The proportion of women in British Columbia (BC) receiving care from a midwife continues to grow and there is a particular focus on promoting and supporting normal pregnancy and birth in the midwifery philosophy of care. In BC, women receiving care from a midwife are less likely to have a caesarean section and other birth interventions. An interpretive approach, based on interpretive phenomenology was used to explore the experiences of midwives in BC of normal birth and the strategies that they use to keep birth normal. Fourteen experienced midwives were purposively selected from across the range of practice, geographical, and rural/urban contexts to participate in depth interviews. Data were analyzed using Thematic Network Analysis. Seven key themes were identified in the data: working with women from the early pregnancy, informing choice, the birth environment, careful watching and waiting, managing early labour, helping the woman to cope with labour, and tools in the tool kit. Midwives in BC work closely with women from early pregnancy to prepare them for a normal birth, and as "instruments of care" they adopt a range of approaches to support women to achieve this. The emphasis on continuity of care in the BC model of midwifery care plays a vital role in this.


Insertion and deletion events that define the pathogen Mycobacterium avium subsp. paratuberculosis.
Mycobacterium avium comprises genetically related yet phenotypically distinct subspecies. Consistent with their common origin, whole-genome sequence comparisons have revealed extensive synteny among M. avium organisms. However, the sequenced strains also display numerous regions of heterogeneity that likely contribute to the diversity of the individual subspecies. Starting from a phylogenetic framework derived by multilocus sequence analysis, we examined the distribution of 25 large sequence polymorphisms across a panel of genetically defined M. avium strains. This distribution was most variable among M. avium subsp. hominissuis isolates. In contrast, M. avium subsp. paratuberculosis strains exhibited a characteristic profile, with all isolates containing a set of genomic insertions absent from other M. avium strains. The emergence of the pathogen from its putative M. avium subsp. hominissuis ancestor entailed the acquisition of approximately 125 kb of novel genetic material, followed by a second phase, characterized by reductive genomics. One genomic deletion is common to all isolates while additional deletions distinguish two major lineages of M. avium subsp. paratuberculosis. For the average strain, these losses total at least 38 kb (sheep lineage) to 90 kb (cattle lineage). This biphasic pattern of evolution, characterized by chromosomal gene acquisition with subsequent gene loss, describes the emergence of M. avium subsp. paratuberculosis and may serve as a general model for the origin of pathogenic mycobacteria.


Prevalence of antibody to hepatitis B core antigen among hepatitis B surface antigen-negative blood donors in Ilorin, Nigeria: A cross-sectional study.
Post-transfusion hepatitis occurs even with stringent donor selection criteria and screening for hepatitis B surface antigen (HBsAg). The objective of this study was to determine the prevalence of antibody to hepatitis B core antigen (anti-HBc) in HBsAg-negative blood donors. This was a cross-sectional study in which 200 HBsAg-negative blood donors were recruited. Screening for viral markers was done using both a rapid test kit and enzyme-linked immunosorbent assay (ELISA) for anti-HBc IgM. Quantitative and qualitative analysis of anti-HBc IgM was done by "capture" enzyme immunoassay using DIA.PRO HBc IgM test kits. The other viral markers were investigated using one step cassette style HBV tests. SPSS version 16 was used for data analysis. A P-value of 0.05 or less was considered significant. There were 190 male (95%) and 10 female (5%) blood donors, with a mean age of 31.7 ± 7.9 years. The prevalence of anti-HBc IgM was 4%. The other viral markers (HBeAg, anti-HBeAg, anti-HBs and total anti-HBc) had a prevalence of 1.5%, 23%, 2.5%, and 32.5%, respectively. The prevalence of anti-HBc IgM in this study was high, and this supports the fact that screening blood donors for HBsAg alone is not sufficient to prevent transmission of HBV.


A meta-analysis of adjusted observational studies and randomized controlled trials of endovascular versus open surgical repair for ruptured abdominal aortic aneurysm.
The aim of the present meta-analysis was to determine whether endovascular aneurysm repair (EVAR) reduces perioperative mortality and improves overall survival compared with open surgical repair (OSR) in patients with ruptured abdominal aortic aneurysm (RAAA). Eligible studies were observational studies with adjusted risk estimates or randomized controlled trials (RCTs) of EVAR versus OSR enrolling individuals with RAAA and reporting perioperative (30-day or in-hospital) or overall (≥3-month) all-cause mortality. Twenty-four adjusted observational studies and 4 RCTs enrolling a total of 56,826 patients with RAAA were identified and included. For perioperative all-cause mortality, pooled analyses of 22 adjusted observational studies and 4 RCTs respectively demonstrated a statistically significant 49% reduction with EVAR relative to OSR (odds ratio [OR]=0.51; 95% confidence interval [CI]: 0.44 to 0.59; P<0.00001) and no statistically significant difference between EVAR and OSR (OR=0.91; 95% CI: 0.68 to 1.22; P=0.53) (P for subgroup differences = 0.0006). For overall (3 months to 8 years) all-cause mortality, a pooled analysis of 7 adjusted observational studies (hazard ratio [HR]=0.92; 95% CI: 0.77 to 1.10; P=0.37) and 3 RCTs (HR=0.89; 95% CI: 0.69 to 1.14; P=0.34) demonstrated no statistically significant difference between EVAR and OSR (P for subgroup differences = 0.81). In patients with RAAA, EVAR is likely effective in prevention of perioperative overall (3 months to 8 years), not all-cause mortality.


The Traditional Model Does Not Explain Attitudes Toward Euthanasia: A Web-Based Survey of the General Public in Finland.
The debate about euthanasia is ongoing in several countries including Finland. However, there is a lack of information on current attitudes toward euthanasia among general Finnish public. The traditional model for predicting individuals' attitudes to euthanasia is based on their age, gender, educational level, and religiosity. However, a new evaluation of religiosity is needed due to the limited operationalization of this factor in previous studies. This study explores the connections between the factors of the traditional model and the attitudes toward euthanasia among the general public in the Finnish context. The Finnish public's attitudes toward euthanasia have become remarkably more positive over the last decade. Further research is needed on the factors that predict euthanasia attitudes. We suggest two different explanatory models for consideration: one that emphasizes the value of individual autonomy and another that approaches euthanasia from the perspective of fears of death or the process of dying.


Comparison of buffy coat preparation to direct method for the evaluation and interpretation of bone marrow aspirates.
Bone marrow differential and French, American, British (FAB) classification of buffy coat preparation (BCP) was compared to direct method (DM) in 69 pediatric patients with various hematologic and oncologic disorders. The marrow evaluation differed significantly in 12 of 69 patients (17.4%). The differential counts were discordant in 9 out of 69 patients (13%), and the FAB classifications were discordant in 3 out of 25 patients (12%) with acute lymphoblastic leukemia (ALL). Underestimation of the percent blasts occurred with buffy coat preparation in patients with acute non-lymphoblastic leukemia (ANLL). While buffy coat preparations can facilitate morphologic evaluation in marrow malignancies, significant errors can occur in determination of the differential count. Direct smear should be used in conjunction with buffy coat smears in the evaluation of bone marrow aspirates.


Structure and Mechanical Performance of Biomimetic Costal Cartilage Models for Ear Framework Handcrafting Simulation.
Ear framework handcrafting simulation using costal cartilage models is crucially important for ear reconstruction surgery education. Fabrication of proper models that are mechanically and structurally comparable to their native counterparts is an unmet challenge. The authors developed structure and mechanical performance biomimetic costal cartilage models for practicing and simulating handcrafting of ear frameworks. High-tensile silicone and three-dimensional techniques were used to fabricate biomimetic models. The models well-replicated the three-dimensional structure of human costal cartilage. Comprehensive mechanical tests showed that high-tensile silicone models had stiffness, hardness, and suture retention ability similar to those of their native counterparts, and they were distinctly superior to commonly used materials for costal cartilage simulation. This model satisfied surgeons and contributed to creation of outstanding ear frameworks. The recreated models were used in ear framework handcrafting workshops. Novices' surgical simulation performance with different models was compared and analyzed. People who used high-tensile silicone models have greater progress and confidence after training. Using high-tensile silicone costal cartilage models is an excellent choice for practicing and simulating the fabrication of ear frameworks manually. The models benefit practitioners and students in practicing handcrafting ear frameworks and surgical skills.


Primary non-gestational mediastinal choriocarcinoma metastatic to the brainstem.
Choriocarcinoma is a highly malignant tumour emerging from the syncytiotrophoblast divided into gestational and non-gestational presentations. Primary choriocarcinoma of the mediastinum is rare. Metastases to the brain often occur; however, brainstem involvement has not been reported for non-gestational choriocarcinoma. We described a middle-aged man who developed a complete left oculomotor nerve paralysis secondary to a brainstem tumour at the midbrain. The workup for the primary source of the brainstem tumour included a chest CT scan, which revealed a mediastinal mass. A mediastinal mass needle biopsy confirmed the diagnosis of primary mediastinal choriocarcinoma. Despite aggressive chemotherapy, the patient died 6 months after the initial presentation from neurological complications and multiorgan failure.


Crohn's disease of the vulva.
Over the past 10 years, it has been well established that Crohn's disease may involve any segment of the gastrointestinal tract from the mouth to the anus and may also cause destructive extraintestinal lesions. Extensive cutaneous ulceration has recently been recognized as one of the rare extraintestinal complications. A case of chronic vulvar ulceration due to Crohn's disease is reported. The clinical manifestations and management of such a lesion are discussed.


Cotton fiber as a model for understanding shifts in cell development under domestication.
Cotton fiber provides the predominant plant textile in the world, and it is also a model for plant cell wall biosynthesis. The development of the single-celled cotton fiber takes place across several overlapping but discrete stages, including fiber initiation, elongation, the transition from elongation to secondary cell wall formation, cell wall thickening, and maturation and cell death. During each stage, the developing fiber undergoes a complex restructuring of genome-wide gene expression change and physiological/biosynthetic processes, which ultimately generate a strikingly elongated and nearly pure cellulose product that forms the basis of the global cotton industry. Here, we provide an overview of this developmental process focusing both on its temporal as well as evolutionary dimensions. We suggest potential avenues for further improvement of cotton as a crop plant.


Paroxysmal atrial fibrillation recognition based on multi-scale Rényi entropy of ECG.
Atrial fibrillation (AF) is a common type of arrhythmia disease, which has a high morbidity and can lead to some serious complications. The ability to detect and in turn prevent AF is extremely significant to the patient and clinician. Using ECG to detect AF and develop a robust and effective algorithm is the primary objective of this study. Some studies show that after AF occurs, the regulatory mechanism of vagus nerve and sympathetic nerve will change. Each R-R interval will be absolutely unequal. After studying the physiological mechanism of AF, we will calculate the Rényi entropy of the wavelet coefficients of heart rate variability (HRV) in order to measure the complexity of PAF signals, as well as extract the multi-scale features of paroxysmal atrial fibrillation (PAF). The data used in this study is obtained from MIT-BIH PAF Prediction Challenge Database and the correct rate in classifying PAF patients from normal persons is 92.48%. The results of this experiment proved that AF could be detected by using this method and, in turn, provide opinions for clinical diagnosis.


Color Doppler sonography with contrast in the differentiation of ovarian tumors.
The objective of this study was to differentiate benign ovarian tumors from malignant ones before surgery using color and pulsed Doppler sonography, and to compare results obtained before and after use of contrast medium, thereby verifying whether contrast results in an improvement in the diagnostic sensitivity. Sixty two women (mean age 49.9 years) with ovarian tumors were studied, 45 with benign and 17 with malignant tumors. All women underwent a transvaginal color Doppler ultrasonographic exam. A study of the arterial vascular flow was made in all tumor areas, as well as an impedance evaluation of arterial vascular flow using the resistance index. Localization of the vessels in the tumor revealed a greater proportion of malignant tumors with detectable internal vascular flows (64%) than benign tumors with such flows (22%). There was a considerable overlap of these findings. The use of contrast identified a greater number of vessels with confirmation in the totality of tumors, but did not improve the Doppler capacity in tumoral differentiation. Malignant tumors presented lower values of resistance index than the benign ones, whether or not contrast was used. The cutoff value for resistance index that better maximized the Doppler sensitivity and specificity was 0.55. Through this value, an increase of the sensitivity after contrast use was obtained, varying from 47% to 82%, while specificity remained statistically unchanged. Although the injection of a microbubble agent improved the sensitivity of the method detecting vascularization of tumors, a positive finding for vascularization by this method was not clinically useful in the differentiation of benign and malignant ovarian tumors.


Janus kinase 2 modulates the lipid-removing but not protein-stabilizing interactions of amphipathic helices with ABCA1.
ABCA1 mediates the transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Apolipoprotein A-I (apoA-I) interactions with ABCA1-expressing cells elicit several responses, including removing cellular lipids, stabilizing ABCA1 protein, and activating Janus kinase 2 (JAK2). Here, we used synthetic apolipoprotein-mimetic peptides to characterize the relationship between these responses. Peptides containing one amphipathic helix of L- or D-amino acids (2F, D-2F, or 4F) and a peptide containing two helices (37pA) all promoted ABCA1-dependent cholesterol efflux, competed for apoA-I binding to ABCA1-expressing cells, blocked covalent cross-linking of apoA-I to ABCA1, and inhibited ABCA1 degradation. 37pA was cross-linked to ABCA1, confirming the direct binding of amphipathic helices to ABCA1. 2F, 4F, 37pA, and D-37pA all stimulated JAK2 autophosphorylation. Inhibition of JAK2 greatly reduced peptide-mediated cholesterol efflux, peptide binding to ABCA1-expressing cells, and peptide cross-linking to ABCA1, indicating that these processes require an active JAK2. In contrast, apoA-I and peptides stabilized ABCA1 protein even in the absence of an active JAK2, implying that this process is independent of JAK2 and lipid efflux-promoting binding of amphipathic helices to ABCA1. These findings show that amphipathic helices coordinate the activity of ABCA1 by several distinct mechanisms that are likely to involve different cell surface binding sites.


Test-retest reliability of the L-Test in patients with advanced knee osteoarthritis.
The reliability of tests to be used in research or clinical practice should be established for each population specific to their intended use. Reliability is important because it allows correct evaluations to be made about treatment effects or about the amount of changes. To evaluate the test-retest reliability and minimal detectable change of the L-test in patients with advanced knee osteoarthritis (OA). The intraclass correlation coefficient (ICC2,1) was used to assess the test-retest reliability of the L-test. The minimal detectable change with 95% confidence interval (MDC95) was calculated to determine the true change. The inclusion criteria were diagnosis of knee OA, had Kellgren Lawrence Grade IV and age of ≥40 years. Twenty-five participants who met the inclusion criteria were included. Five were male and the mean age was 62.32±9.77 years. All of the participants had radiographic findings indicative of Kellgren-Lawrence Grade IV. The L-test showed excellent test-retest reliability. The ICC was 0.99, the SEM and the MDC95 was 1,90 and 5.28 seconds, respectively. The L-test is a reliable outcome measurement for the assessment of walking ability in patients with advanced knee OA, and it showed very high test-retest reliability in these patients. This test may assist clinicians and researchers in assessing the functional mobility of patients and planning rehabilitation in patients with advanced knee OA.


Classifying Hydroceles of the Pelvis and Groin: An Overview of Etiology, Secondary Complications, Evaluation, and Management.
A hydrocele is defined as the pathological buildup of serous fluid in the pelvis and groin due to various etiologies such as diseases or trauma. It has distinct clinical manifestations, particularly discomfort and psychosocial distress. Understanding the anatomy, embryology, and physiology associated with hydrocele formation is crucial to understand its onset and progression. A MEDLINE® search was conducted using keywords for the relevant classification of hydrocele and its etiology, complications, sexual barriers, evaluation, and management. Appropriately classifying the hydrocele as primary, secondary communicating, secondary noncommunicating, microbe-induced, inflammatory, iatrogenic, trauma-induced, tumor-induced, canal of Nuck, congenital, and giant is important for identifying the underlying etiology. Often this process is overlooked when the classification or etiology is too rare. A focused evaluation is important for this, so that timely management can be provided. We comprehensively review the classifications, etiology, and secondary complications of hydrocele. Pitfalls of current diagnostic techniques are explored along with recommended methods for accurate diagnosis and current treatment options. Due to the range of classifications and etiologies of hydrocele in the pelvis and groin, a deliberate differential diagnosis is essential to avoiding imminent life-threatening complications as well as providing the appropriate treatment.


Farmer perceptions and willingness to pay for novel livestock pest control technologies: A case of tsetse repellent collar in Kwale County in Kenya.
Tsetse-transmitted Animal African Trypanosomosis (AAT) is one of the most important constraints to livestock development in Africa. Use of trypanocides has been the most widespread approach for the management of AAT, despite the associated drug resistance and health concerns associated with drug metabolites in animal products. Alternative control measures that target tsetse fly vectors of AAT, though effective, have been hard to sustain in part because these are public goods applied area-wide. The International Centre of Insect Physiology and Ecology (icipe) and partners have developed and implemented a novel tsetse repellent collar (TRC) applied on animals to limit contact of tsetse flies and livestock, thereby reducing AAT transmission. The TRC has now advanced to commercialization. A household-level survey involving 632 cattle keeping households, was conducted in Shimba Hills region of Kwale County, where field trials of the TRC have been previously conducted to assess farmers' knowledge, perception, and practices towards the management of tsetse flies, their willingness to pay (WTP) for the TRC, and factors affecting the WTP. Almost all the respondents (90%) reported that tsetse flies were the leading cattle infesting pests in the area. About 22% of these correctly identified at least four AAT clinical signs, and even though many (68%) used trypanocidal drugs to manage the disease, 50% did not perceive the drug as being effective in AAT management (50%). Few respondents (8%) were aware of the harmful effects of trypanocidal drugs. About 89% of the respondents were aware of icipe TRC, and 30% of them were using the field trial collars during the survey. Sixty-three (63%) of them were willing to pay for the TRC at the same cost they spend treating an animal for AAT. On average farmers were willing to pay KES 3,352 per animal per year. Male educated household heads are likely to pay more for the TRC. Moreover, perceived high AAT prevalence and severity further increases the WTP. Wider dissemination and commercialization of the herd-level tsetse control approach (TRC) should be encouraged to impede AAT transmission and thus enhance food security and farm incomes among the affected rural communities. Besides the uptake of TRC can be enhanced through training, especially among women farmers.


Engineering Escherichia coli as a platform for the in vivo synthesis of prenylated aromatics.
Prenylated aromatics (PAs) are an important class of natural products with valuable pharmaceutical applications. To address current limitations of their sourcing from plants, here, we present a microbial platform for the in vivo synthesis of PAs based on the aromatic prenyltransferase NphB from Streptomyces sp. strain CL190. As proof of concept, we targeted the prenylation of phenolic/phenolcarboxylic acids, including orsellinic (OSA), divarinolic (DVA), and olivetolic (OLA) acids, whose prenylated products have important biopharmaceutical applications. Although the ability of wild-type NphB to catalyze the prenylation reaction with each acid was validated by in vitro characterization, improvement of product titers in vivo required protein modeling and rational design to engineer NphB variants with increased activity and product selectivity. When a designed NphB variant with eightfold improved catalytic efficiency toward OSA was expressed in an Escherichia coli host engineered to generate geranyl pyrophosphate at high flux through the mevalonate pathway, we observed up to 300 mg/L prenylated products by exogenously supplying OSA. The improved properties of engineered NphB were also utilized to demonstrate the diversification of this in vivo platform by using both different aromatic acceptors and different prenyl donors to generate various PA compounds, including medicinally important compounds such as cannabigerovarinic, cannabigerolic, and grifolic acids.


Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.
The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement. The neurobiological basis for these effects is poorly understood. Here, we examine how in utero exposure to heroin affects brain development into early adolescence in a mouse model. Pregnant C57BL/6J mice received escalating doses of heroin twice daily on gestational days 4-18. The brains of offspring were assessed on postnatal day 28 using 9.4 T diffusion MRI of postmortem specimens at 36 μm resolution. Whole-brain volumes and the volumes of 166 bilateral regions were compared between heroin-exposed and control offspring. We identified a reduction in whole-brain volume in heroin-exposed offspring and heroin-associated volume changes in 29 regions after standardizing for whole-brain volume. Regions with bilaterally reduced standardized volumes in heroin-exposed offspring relative to controls include the ectorhinal and insular cortices. Regions with bilaterally increased standardized volumes in heroin-exposed offspring relative to controls include the periaqueductal gray, septal region, striatum, and hypothalamus. Leveraging microscopic resolution diffusion tensor imaging and precise regional parcellation, we generated whole-brain structural MRI diffusion connectomes. Using a dimension reduction approach with multivariate analysis of variance to assess group differences in the connectome, we found that in utero heroin exposure altered structure-based connectivity of the left septal region and the region that acts as a hub for limbic regulatory actions. Consistent with clinical evidence, our findings suggest that prenatal opioid exposure may have effects on brain morphology, connectivity, and, consequently, function that persist into adolescence. This work expands our understanding of the risks associated with opioid misuse during pregnancy and identifies biomarkers that may facilitate diagnosis and treatment.


An intrapartum calculator for predicting cesarean birth due to dystocia: Preliminary findings from a single-center study in Korea.
Previous calculators based on antepartum or pre-labor factors preclude intrapartum counseling. We aimed to develop a reliable, programmable, intrapartum calculator to predict the risk of cesarean birth (CB) due to dystocia and to increase the discriminatory accuracy of the predictive model. Data were obtained retrospectively for 1326 singleton term deliveries with cephalic presentation. Two predictive multivariable logistic regression analysis models were constructed using pre-active labor variables alone (model A) or with active labor variables (model B). The discriminatory accuracies and goodness-of-fit of the models were compared using receiver operating characteristic (ROC) curves or -2log-likelihood ratios, Akaike information criterion (AIC), and Bayesian information criterion (BIC), respectively. Both models were internally validated using a bootstrapping procedure. Model A yielded an area under the curve (AUC) of 0.859 and adequate goodness of fit (P = 0.970). Model B yielded a significantly higher AUC of 0.887 and adequate goodness of fit (P = 0.624), as well as a significantly lower AIC and BIC (P < 0.001). Internal validation revealed a minimal optimism of 0.0070491 and 0.0068976 for models A and B, respectively. Finally, the logistic regression equations were converted into programmable calculators to yield easy-to-understand basic (model A) and additional intrapartum CB calculators (model B). The programmable calculators developed herein can augment intrapartum counseling. Our findings suggest that the risk of CB due to dystocia during labor should be estimated using a calculator that corresponds to labor progression. Further studies should explore external validation of these statistical models before translation to a clinical setting.


Genetic variations of body weight and GCRV resistance in a random mating population of grass carp.
The grass carp (Ctenopharyngodon idellus) is an important species in freshwater aquaculture both in China and on a global scale. Variety degeneration and frequent diseases have limited the further development of grass carp aquaculture. Thus, new and improved varieties are required. Here, we identified and assessed the body weight and disease resistance in a random mating population of 19 ♀ × 22 ♂ grass carp, which were derived from different water systems. In both the growth experimental group of 10,245 fish and grass carp reovirus (GCRV)-infected group with 10,000 fish, 78 full-sib families were statistically analyzed for body weight and GCRV resistance. The findings showed that body weight traits had low heritability (0.11 ± 0.04, 0.10 ± 0.03 and 0.12 ± 0.05), GCRV resistance traits had high heritability (0.63 ± 0.11); body weight was higher in 3 families, whereas GCRV resistance was significantly greater in 11 families. Our results confirmed that the natural germplasm resources of wild grass carp were genetically diverse. Breeding of GCRV resistant varieties of grass carp have better genetic basis. This study provides the basis for constructing basal populations for grass carp selective breeding, quantitative trait loci (QTL) and genome-wide association studies (GWAS) analysis.


Drug-specificity in the perturbation of pulmonary disposition of serotonin in rabbit in vivo.
Previous work indicates that one consequence of the accumulation of several xenobiotics in the lung is compromised pulmonary disposition of 5-hydroxytryptamine (5-HT). In the present studies, we examined whether pulmonary accumulation of chlorpromazine (CPZ), propranolol (P), imipramine (IMP), and clomipramine (Cl-IMP) affected 5-HT disposition in rabbit lungs. Pulmonary extraction and metabolism of [14C]-5-HT during single pulmonary passage were examined using the reference indicator radioisotope dilution technique in male New Zealand albino rabbits. After control experiment, animals received CPZ or P (2.5, 5, or 10 mg/kg), IMP or Cl-IMP (0.25, 0.5 or 1.0 mg/kg) via the jugular vein. Pulmonary clearance was 83% of administered 5-HT. A significant proportion (28%) of total radioactivity in the bloodstream after single passage was recovered as 5-HIAA in control experiments. These values were reduced significantly to 70 and 20%, respectively upon prior administration of IMP (0.25 mg/kg). Cl-IMP was more effective in reducing these values further. CPZ and P were marginally effective at the highest dose. While prior administration of IMP and Cl-IMP resulted in pulmonary accumulation of both drugs, the latter accumulated to a significantly greater extent. These results suggest that Cl-IMP has higher affinity to the rabbit lung than IMP and may inhibit pulmonary uptake of 5-HT by competition for uptake and binding sites more than IMP.


Monitoring the distribution and dynamics of signaling microdomains in living cells with lipid-specific probes.
Specialized lipid microdomains in the cell plasma membrane, referred to as 'lipid rafts', are enriched in sphingolipids and cholesterol and have drawn considerable interest as platforms for the recruitment of signaling molecules. Despite numerous biochemical and cellular studies, debate persists on the size, lifetime and even the existence of lipid rafts, emphasizing the need for reliable lipid probes to study in situ membrane lipid organization. In this review, we summarize our recent data on living cells using two specific probes of raft components: lysenin, a sphingomyelin- binding protein and the fluorescein ester of poly(ethyleneglycol)cholesteryl ether that labels cholesterol-rich domains. Sphingomyelin-rich domains that are spatially and functionally distinct from the GM1 ganglioside-rich domains were found at the plasma membrane of Jurkat T cells. In addition, the dynamics of cholesterol-rich domains could be monitored at the cell surface as well as inside the cells.


Behind the Scenes: Care Coordination Time in an Outpatient Pediatric Palliative Oncology Clinic.
Background: Integrated pediatric palliative oncology (PPO) outpatient models are emerging to assist oncologists, children, and families throughout their course with cancer. Significant time is devoted to care coordination ("nonbillable" time), but the scope, time per patient, and ratio of nonbillable to billable (NB:B) minutes are unknown. This information is crucial to designing new PPO outpatient clinics and advocating for appropriate personnel, physician time, and resources. Our objectives were to quantify nonbillable time and evaluate demographic or disease-based associations. Methods: A single-institution one-day PPO clinic was started in July 2017. All encounters were tracked for 11 months. Administrative and PPO inpatient time were excluded. Billable and nonbillable minutes were recorded daily. Ratios of NB:B minutes by patient demographics and clinical factors were calculated using descriptive statistics and multivariate modeling. Results: Ninety-five patients were included [solid tumors (42, 44%), brain tumors (33, 35%), and leukemia/lymphoma (20, 21%)]. PPO completed billable visits on 52 of 95 (55%) patients and assisted without billing in the care of 43 patients (45%). Twenty-four (25%) patients were deceased. Overall NB:B ratio was 1.04 and differed among diagnoses (leukemia/lymphoma 2.5, solid tumor 0.9, and brain tumor 0.8). Deceased patients had a higher ratio of NB:B minutes than alive patients (1.9 vs. 0.8, p = 0.012). Billable and nonbillable minutes both increased over time. Conclusions: Care coordination in a PPO clinic is time intensive and grows with clinic volume. When devising a PPO outpatient program, this NB:B ratio should be accounted for in clinician time and personnel devoted to patient and family assistance.


Accelerated second-degree baccalaureate nursing programs: what is the significance of clinical instructors?
Accelerated second-degree nursing programs are a popular method of entry into nursing for many individuals beginning a second career in nursing. Using a hermeneutic phenomenological approach, this study analyzed the experiences of 19 accelerated second-degree baccalaureate nursing graduates to understand how their student experiences best prepared them for nursing practice after graduation. The significance of clinical instructors to students' development as nurses was revealed in the data analysis and identified in the theme, Blending Practice and Pedagogy. This article describes the implications of this theme for both accelerated second-degree nursing programs and faculty recruitment and retention.


Describing and characterising on-demand delivery of unhealthy commodities in New Zealand.
To determine the geographical location and characteristics of on-demand delivery services operating in New Zealand. We systematically searched the web and application (app) stores for on-demand services offering rapid delivery of food, alcohol, cigarettes or vaping products in New Zealand and mapped their geographic location as of May 2021. Using desktop review, data on service characteristics were collected and stratified including: types of commodities available, promotion strategies, and the legal aspects of access to age-restricted items. On-demand services for food, alcohol and nicotine products operate across urban and rural New Zealand. All services offered personal memberships and 97% used promotions. All services offering restricted items had an age verification process, however, only 87% had birth date entry and 73% had an 18+ message pop-up on website entry. Only 60% of services appeared to have number limits on restricted items. Much of New Zealand is serviced by on-demand delivery services. The trend towards on-demand delivery services may increase unhealthy food, alcohol and nicotine-related harms and it undermines current government actions, e.g. the Smokefree 2025 goal. This research informs policy to reduce the future health burden.